Migraine Management: Acute and Preventive Treatment
Acute Treatment Algorithm
For mild-to-moderate migraine, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) or acetaminophen 1000 mg; for moderate-to-severe attacks or when NSAIDs fail after 2-3 episodes, escalate to combination therapy with a triptan plus NSAID, which provides superior efficacy compared to either agent alone. 1
First-Line Acute Treatment
NSAIDs are the recommended first-line therapy for mild-to-moderate migraine attacks, with ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 1000 mg providing the strongest evidence. 1
Treat early during the attack while pain is still mild to maximize effectiveness; early treatment significantly improves pain-free rates at 2 hours and sustained pain-free outcomes during 24 hours compared to treating established moderate-to-severe pain. 1, 2
Limit all acute medications to no more than 2 days per week (approximately 10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1
Second-Line: Triptans
Triptans are first-line for moderate-to-severe migraine or when NSAIDs fail after 2-3 episodes, with oral sumatriptan 50-100 mg, rizatriptan 10 mg, or eletriptan 40 mg providing the strongest evidence. 1
Combination therapy with sumatriptan 50-100 mg PLUS naproxen sodium 500 mg is superior to either agent alone, achieving 130 more patients per 1000 with sustained pain relief at 48 hours and 90 more patients per 1000 with pain relief at 2 hours. 1
If one triptan fails after 2-3 headache episodes, try a different triptan before abandoning the class entirely, as failure of one does not predict failure of others; rizatriptan 10 mg reaches peak concentration fastest (60-90 minutes), eletriptan 40 mg and zolmitriptan 2.5-5 mg reportedly have fewer adverse reactions than sumatriptan, and naratriptan has the longest half-life which may decrease recurrence. 1
For rapid progression to peak intensity or significant nausea/vomiting, use subcutaneous sumatriptan 6 mg, which provides the highest efficacy (59% pain-free at 2 hours) with onset within 15 minutes, compared to 50-67% response for oral formulations. 1, 3
Intranasal sumatriptan 5-20 mg or other nasal spray triptans are particularly useful when significant nausea or vomiting is present early in the attack. 1
Third-Line: CGRP Antagonists (Gepants)
Ubrogepant 50-100 mg or rimegepant are third-line options for moderate-to-severe migraine when triptans are contraindicated or after failure of triptan-NSAID combinations; these agents have no vasoconstriction, making them safe for patients with cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease. 1
Limit ubrogepant use to no more than 8 migraine attacks per 30-day period to prevent medication-overuse headache. 1
Parenteral Options for Severe Attacks
For emergency department or urgent care presentations, use metoclopramide 10 mg IV plus ketorolac 30 mg IV as first-line combination therapy, providing rapid pain relief while minimizing side effects and rebound headache risk. 1
Dihydroergotamine (DHE) 0.5-1.0 mg IV has good evidence for efficacy as monotherapy when NSAIDs are contraindicated, and can be repeated every hour up to a maximum of 2 mg IV per day. 1
Prochlorperazine 10 mg IV effectively relieves headache pain and is comparable to metoclopramide in efficacy. 1
Contraindications and Critical Pitfalls
Triptans are absolutely contraindicated in patients with ischemic heart disease, previous myocardial infarction, coronary artery vasospasm, uncontrolled hypertension, cerebrovascular disease, history of stroke or TIA, or basilar/hemiplegic migraine. 1
Never use opioids (hydromorphone, oxycodone, codeine) or butalbital-containing compounds for migraine treatment due to questionable efficacy, high risk of medication-overuse headache (two-fold higher than NSAIDs/triptans), dependency, rebound headaches, and loss of efficacy over time; reserve opioids exclusively for cases where every other evidence-based treatment is contraindicated, sedation is acceptable, and abuse risk has been formally assessed. 1
Do not allow patients to increase frequency of acute medication use in response to treatment failure, as this creates a vicious cycle of medication-overuse headache; instead transition to preventive therapy while optimizing acute treatment strategy. 1
Preventive Therapy Algorithm
Initiate preventive therapy for patients with ≥2 migraine attacks per month producing disability lasting ≥3 days, use of abortive medication more than twice per week, contraindication to or failure of acute treatments, or uncommon migraine conditions. 4
First-Line Preventive Medications
Propranolol 80-240 mg/day or timolol 20-30 mg/day are first-line beta-blockers with strong randomized controlled trial evidence for migraine prevention. 4
Topiramate 50-100 mg/day (typically 50 mg twice daily) is the only oral preventive with strong RCT evidence specifically for chronic migraine and is preferred in patients with obesity due to associated weight loss. 4
Candesartan is a first-line agent particularly useful for patients with comorbid hypertension. 4
Second-Line Preventive Medications
Amitriptyline 30-150 mg/day is preferred for patients with comorbid depression, anxiety, or sleep disturbances, as it treats both migraine and mood disorders simultaneously; however, it lacks robust RCT evidence for chronic migraine prophylaxis and its efficacy is mainly demonstrated in episodic migraine. 4
Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day are effective but strictly contraindicated in women of childbearing potential due to teratogenic effects; contraception counseling is mandatory if these agents are considered. 4
Third-Line: CGRP Monoclonal Antibodies and OnabotulinumtoxinA
CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered when 2-3 oral preventive medications have failed or are contraindicated, administered monthly via subcutaneous injection, with efficacy assessed after 3-6 months. 4
OnabotulinumtoxinA is the only FDA-approved preventive therapy specifically for chronic migraine (not episodic migraine), administered as 155-195 U injected across 31-39 sites every 12 weeks, with efficacy evaluated after 6-9 months; it reduces headache days, episodes, cumulative hours, and improves quality of life in chronic migraine patients. 1, 4
Implementation Strategy
Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases, allowing an adequate trial period of 2-3 months for oral agents, 3-6 months for CGRP monoclonal antibodies, and 6-9 months for onabotulinumtoxinA. 4
Use headache diaries (paper or smartphone) to track attack frequency, severity, duration, disability, treatment response, and adverse effects; this validated tool improves accuracy of reporting and helps identify modifiable triggers. 1, 4
Consider pausing preventive treatment after 6-12 months of successful therapy to determine if it can be discontinued; a useful measure is calculating the percentage reduction in monthly migraine days, with ≥50% reduction considered successful. 4
Common Pitfalls in Preventive Therapy
Failing to recognize medication-overuse headache from frequent use of acute medications (≥10 days/month for triptans or ≥15 days/month for NSAIDs) before starting preventive therapy; MOH must be addressed first through abrupt cessation of overused medications. 1, 4
Inadequate duration of preventive trial (less than 2-3 months for oral agents) before declaring treatment failure. 4
Starting with too high a dose, leading to poor tolerability and discontinuation; always start low and titrate slowly. 4
Lifestyle Modifications and Trigger Management
Identify and systematically modify triggers including sleep deprivation, stress, tobacco use, alcohol consumption, excessive caffeine intake, irregular meals, and dehydration through headache diary tracking. 1, 4
Weight loss reduces migraine frequency in patients with obesity. 4
Screen and treat obstructive sleep apnea to reduce migraine frequency. 4
Implement stress management through behavioral interventions (cognitive behavioral therapy, biofeedback, relaxation training) to modify responses to stressful events; these can be offered alongside medication as effective adjuncts. 4
Special Populations and Considerations
Children and Adolescents
Use ibuprofen to treat pain in children/adolescents; in adolescents consider sumatriptan/naproxen oral, zolmitriptan nasal, sumatriptan nasal, rizatriptan ODT, or almotriptan oral. 5
Discuss with patients/families whether to use a preventive medication, since placebo was as effective as the studied medication in many pediatric trials. 5
For prevention, discuss evidence for amitriptyline combined with cognitive behavioral therapy, topiramate, and propranolol; when relevant, discuss teratogenic effects of topiramate and valproate and advise effective birth control methods plus folate supplementation. 5
Chronic Migraine with Medication-Overuse Headache
Abrupt cessation of both overused triptans and NSAIDs is recommended; evidence does not support gradual taper, though patients should be warned that headache intensity may temporarily worsen for 2-10 days during withdrawal. 1
Do not substitute another acute medication during withdrawal, as this merely transfers the overuse to a different agent. 1
Initiate onabotulinumtoxinA as first-line preventive when three oral preventives have failed, as it is the only FDA-approved therapy specifically for chronic migraine. 1
Post-withdrawal, reserve acute treatment for the most severe attacks and strictly limit to ≤2 days per week to prevent recurrence of MOH. 1
Uncontrolled Hypertension
Acetaminophen 1000 mg is the safest first-line analgesic when hypertension is uncontrolled, as NSAIDs can further elevate blood pressure and increase cardiovascular risk. 1
After blood pressure control, NSAIDs may be reconsidered as they demonstrate superior efficacy to acetaminophen for most headache types. 1